The exon junction complex component Magoh controls brain size by regulating neural stem cell division.

Silver, Debra L

Watkins-Chow, Dawn E

Schreck, Karisa C

Pierfelice, Tarran J

Larson, Denise M

Burnetti, Anthony J

Liaw, Hung-Jiun

Myung, Kyungjae

Walsh, Christopher A

Gaiano, Nicholas

Pavan, William J

United States

2017-04-26T18:25:13Z

2017-04-26T18:25:13Z

2010-05

Brain structure and size require precise division of neural stem cells (NSCs), which self-renew and generate intermediate neural progenitors (INPs) and neurons. The factors that regulate NSCs remain poorly understood, and mechanistic explanations of how aberrant NSC division causes the reduced brain size seen in microcephaly are lacking. Here we show that Magoh, a component of the exon junction complex (EJC) that binds RNA, controls mouse cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly because of INP depletion and neuronal apoptosis. Defective mitosis underlies these phenotypes, as depletion of EJC components disrupts mitotic spindle orientation and integrity, chromosome number and genomic stability. In utero rescue experiments showed that a key function of Magoh is to control levels of the microcephaly-associated protein Lis1 during neurogenesis. Our results uncover requirements for the EJC in brain development, NSC maintenance and mitosis, thereby implicating this complex in the pathogenesis of microcephaly.

https://www.ncbi.nlm.nih.gov/pubmed/20364144

nn.2527

1546-1726

https://hdl.handle.net/10161/14117

eng

Springer Science and Business Media LLC

Nat Neurosci

10.1038/nn.2527

1-Alkyl-2-acetylglycerophosphocholine Esterase

Age Factors

Animals

Animals, Newborn

Apoptosis

Brain

Bromodeoxyuridine

Cell Differentiation

Cell Division

DNA Mutational Analysis

Embryo, Mammalian

Eye Proteins

Gene Expression Profiling

Gene Expression Regulation, Developmental

Genotype

Green Fluorescent Proteins

HeLa Cells

Homeodomain Proteins

Humans

In Situ Nick-End Labeling

Mice

Mice, Inbred C57BL

Mice, Transgenic

Microcephaly

Microtubule-Associated Proteins

Mutation

Nerve Tissue Proteins

Neurogenesis

Neurons

Nuclear Proteins

Oligonucleotide Array Sequence Analysis

Organ Size

PAX6 Transcription Factor

Paired Box Transcription Factors

RNA Interference

RNA, Messenger

Repressor Proteins

Stem Cells

T-Box Domain Proteins

Transfection

The exon junction complex component Magoh controls brain size by regulating neural stem cell division.

Journal article

Silver, Debra L|0000-0001-9189-844X

https://www.ncbi.nlm.nih.gov/pubmed/20364144

551

558

5

Basic Science Departments

Cell Biology

Duke

Duke Cancer Institute

Duke Institute for Brain Sciences

Institutes and Centers

Institutes and Provost's Academic Units

Molecular Genetics and Microbiology

Neurobiology

School of Medicine

University Institutes and Centers

Published

13